Mueller, Nike, Schulte, Dominik M., Hillebrand, Susann, Tuerk, Kathrin, Hampe, Jochen, Schafmayer, Clemens, Brosch, Mario, von Schoenfels, Witigo, Ahrens, Markus, Zeuner, Rainald, Schroeder, Johann O., Blueher, Matthias, Gutschow, Christian, Freitag-Wolf, Sandra, Stelmach-Mardas, Marta, Saggau, Carina, Schreiber, Stefan and Laudes, Matthias (2014) B Lymphocyte Stimulator (BLyS) Is Expressed in Human Adipocytes In Vivo and Is Related to Obesity but Not to Insulin Resistance. PLoS ONE, 9 (4).

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Abstract

Inflammation and metabolism have been shown to be evolutionary linked and increasing evidence exists that pro-inflammatory factors are involved in the pathogenesis of obesity and type 2 diabetes. Until now, most data suggest that within adipose tissue these factors are secreted by cells of the innate immune system, e. g. macrophages. In the present study we demonstrate that B lymphocyte stimulator (BLyS) is increased in human obesity. In contrast to several pro-inflammatory factors, we found the source of BLyS in human adipose tissue to be the adipocytes rather than immune cells. In grade 3 obese human subjects, expression of BLyS in vivo in adipose tissue is significantly increased (p<0.001). Furthermore, BLyS serum levels are elevated in grade 3 human obesity (862.5+222.0 pg/ml vs. 543.7+60.7 pg/ml in lean controls, p<0.001) and are positively correlated to the BMI (r = 0.43, p<0.0002). In the present study, bariatric surgery significantly altered serum BLyS concentrations. In contrast, weight loss due to a very-low-calorie-formula-diet (800 kcal/d) had no such effect. To examine metabolic activity of BLyS, in a translational research approach, insulin sensitivity was measured in human subjects in vivo before and after treatment with the human recombinant anti-BLyS antibody belimumab. Since BLyS is known to promote B-cell proliferation and immunoglobulin secretion, the present data suggest that adipocytes of grade 3 obese human subjects are able to activate the adaptive immune system, suggesting that in metabolic inflammation in humans both, innate and adaptive immunity, are of pathophysiological relevance.

Document Type:	Article
Additional Information:	Times Cited: 0 Laudes, Matthias/C-8885-2011; Hampe, Jochen/A-2555-2010 Hampe, Jochen/0000-0002-2421-6127 0
Research affiliation:	Kiel University OceanRep > The Future Ocean - Cluster of Excellence
Publisher:	Public Library of Science
Projects:	Future Ocean
Date Deposited:	30 Mar 2015 12:35
Last Modified:	30 Mar 2015 12:35
URI:	https://oceanrep.geomar.de/id/eprint/28080

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